The current inability to effectively deliver corrective doses of lysosomal enzymes to key cells involved in cardiovascular and cerebrovascular disease remains a significant hurdle for rare lysosomal disorders (LSD) such as Fabry disease and other diseases with significant cardiovascular pathologies. BioStrategies LC is developing the plant lectin RTB as a carrier capable of expanding enzyme delivery to ?hard-to-treat? organs and tissues including heart, brain, and bone. Lectin mediated ERT delivery has recently shown promise in other LSDs including MPS I and GM1. This SBIR is focused on developing a ?delivery-enhanced? enzyme replacement therapy (ERT) for patients with Fabry disease. Fabry is a X-linked LSD caused by genetic deficiencies in alpha- galactosidase A (?-GalA) leading to severe multi-organ pathologies with cardiac death, followed by stroke, as the leading causes of death. Fabry disease has emerged as the key LSD model for heart disease due to extensive cardiomyopathy and other cardiovascular presentations. Our long-term goal is to bring an ERT capable of treating the full spectrum of progressive cardiac and other disease manifestations to Fabry patients. Objectives of this Phase I SBIR feasibility study are to produce bioactive ?- GalA:RTB fusions and demonstrate product delivery into human myocytes, correction of lysosomal phenotype in Fabry cells, and biodistribution to heart and other tissues in the Fabry mouse model. Success in Phase I feasibility goals will support moving on to rigorous Phase II SBIR follow-up preclinical assessments aimed at moving this promising ERT product to an IND. The feasibility established here will also support expanding the RTB carrier system to other ERTs and therapeutics for diseases having life-threatening cardiovascular involvement.